A Phase I / II Trial of Nintedanib in Asian Hepatocellular Carcinoma Patients

Carcinoma, Hepatocellular Clinical Trial

Official title:

A Multicenter, Open Label, Phase I/Randomized II Study to Evaluate Safety, Pharmacokinetics and Efficacy of BIBF 1120 in Comparison With Sorafenib for Advanced Hepatocellular Carcinoma Patients in Asia.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00987935
• Other study ID #: 1199.39
• Status: Completed
• Phase: Phase 2
• First received: September 30, 2009
• Last updated: February 9, 2016
• Start date: October 2009
• Est. completion date: January 2016

Study information

• Verified date: February 2016
• Source: Boehringer Ingelheim
• Contact: n/a
• Is FDA regulated: No
• Health authority: South Korea: Ministry of Food and Drug Safety (MFDS)Taiwan: Department of HealthUnited States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

This study is to evaluate the safety, appropriate dose, and efficacy of BIBF 1120 in liver cancer patients

Recruitment information / eligibility

• Status: Completed
• Enrollment: 134
• Est. completion date: January 2016
• Est. primary completion date: July 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion criteria:

1. Hepatocellular carcinoma, either histologically/cytologically confirmed or clinically diagnosed, which is not amenable to curative surgery or loco-regional therapy

2. Age 18 years or older

3. Eastern Cooperative Group performance score of 2 or less

4. Child-Pugh score of 7 or less

5. Written informed consent in accordance with International Conference on Harmonisation (ICH) and Good Clinical Practice (GCP) and local legislation

Exclusion criteria:

1. Prior systemic therapy for metastatic/unresectable hepatocellular carcinoma (for phase II)

2. More than one line of prior systemic therapy for metastatic/unresectable hepatocellular carcinoma (for phase I)

3. Uncontrolled or refractory ascites to adequate medical therapy

4. Bilirubin greater than 1.5 times upper limit of normal

5. Aspartate amino transferase or alanine amino transferase greater than 5 times upper limit of normal

6. Absolute neutrophil count less than 1500/microliter

7. Platelet count less than 75000/microliter

8. Hemoglobin less than 9 g/dL

9. Serum creatinine greater than 1.5 times upper limit of normal

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Hepatocellular

Intervention

Drug:
• Sorafenib
400 mg twice daily
• BIBF 1120
Twice daily

Locations

Country	Name	City	State
Korea, Republic of	1199.39.82001 Boehringer Ingelheim Investigational Site	Seoul
Korea, Republic of	1199.39.82002 Boehringer Ingelheim Investigational Site	Seoul
Korea, Republic of	1199.39.82003 Boehringer Ingelheim Investigational Site	Seoul
Korea, Republic of	1199.39.82004 Boehringer Ingelheim Investigational Site	Seoul
Korea, Republic of	1199.39.82005 Boehringer Ingelheim Investigational Site	Seoul
Korea, Republic of	1199.39.82006 Boehringer Ingelheim Investigational Site	Seoul
Taiwan	1199.39.88606 Boehringer Ingelheim Investigational Site	Changhua
Taiwan	1199.39.88609 Boehringer Ingelheim Investigational Site	Kaohsiung
Taiwan	1199.39.88610 Boehringer Ingelheim Investigational Site	Kaohsiung
Taiwan	1199.39.88605 Boehringer Ingelheim Investigational Site	Taichung
Taiwan	1199.39.88602 Boehringer Ingelheim Investigational Site	Tainan
Taiwan	1199.39.88608 Boehringer Ingelheim Investigational Site	Tainan City
Taiwan	1199.39.88601 Boehringer Ingelheim Investigational Site	Taipei
Taiwan	1199.39.88603 Boehringer Ingelheim Investigational Site	Taipei
Taiwan	1199.39.88604 Boehringer Ingelheim Investigational Site	Taoyuan County
Taiwan	1199.39.88607 Boehringer Ingelheim Investigational Site	Yunlin County

Sponsors (1)

Lead Sponsor	Collaborator
Boehringer Ingelheim

Countries where clinical trial is conducted

Korea, Republic of,  Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximum Tolerated Dose in Phase I	The MTD was defined as the highest dose studied for which the incidence of DLTs was 0/3 or less than 2/6 patients during the first treatment course.	4 weeks	No
Primary	Time to Progression (TTP) in Phase II	TTP according to Response Evaluation Criteria in Solid Tumours (RECIST) 1.0 criteria based on central independent review. TTP RECIST 1.0 was defined as the time from randomisation to disease progression according to RECIST 1.0.	From randomization until data cut-off (28 Sep 2012); Up to 77 weeks	No
Secondary	Time to Progression (TTP) in Phase II (Follow-up Analyses)	TTP according to Response Evaluation Criteria in Solid Tumours (RECIST) 1.0 criteria based on central independent review. TTP RECIST 1.0 was defined as the time from randomisation to disease progression according to RECIST 1.0.	From randomization until disease progression or data cut-off (16 Jul 2014); Up to 171 weeks	No
Secondary	Incidence and Intensity of Adverse Events (AEs) Reported as the Number of Patients With AEs According to Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0 Throughout the Treatment Period.	Incidence and worst intensity (severity) of Adverse Events with grading according to the Common Terminology Criteria for Adverse Events (CTCAE version 3.0).	AEs with an onset during therapy with study treatment or within 28 days after discontinuation of study treatment (up to 1066 days)	No
Secondary	Incidence of Dose Limiting Toxicity in Phase I	Number of patients with dose limiting toxicity are presented	4 weeks	No
Secondary	Objective Tumour Response by RECIST	Objective RECIST 1.0 tumour response was defined as Complete Response (CR) or Partial Response (PR) and was derived from the patient's best objective RECIST 1.0 response based on central independent review.; 95% Confidence Interval presented below are computed by Clopper and Pearson method.	From randomization until data cut-off (16 July 2014); Up to 171 weeks	No
Secondary	Progression Free Survival (PFS)	PFS by RECIST 1.0 was defined as the duration from date of randomisation to date of progression or death, whichever occurred earlier, based on central independent review.	From randomization until data cut-off (16 July 2014); Up to 171 weeks	No
Secondary	Overall Survival	Overall survival was defined as the duration from date of randomisation to the date of death.	From randomization until data cut-off (16 July 2014); Up to 171 weeks	No
Secondary	AUC0-12,ss,Norm (Area Under the Plasma Concentration-time Curve Between 0 and 12 Hours at Steady State, Normalised Values) of Nintedanib	AUC0-12,ss,norm (area under the plasma concentration-time curve between 0 and 12 hours at steady state, normalised values) of Nintedanib; Detailed time points of sampling are: Phase I and selected phase II patients in the Nintedanib arm: Cycle 1, Day 15 to 16: Immediately prior to swallowing the dose of nintedanib (predose) and 1 hour (h), 2 h, 3 h, 4 h, 5 h, 7 h, 10 h, 12 h and 24 h after drug administration on Day 15; Cycle 2, Day 1: Immediately prior to swallowing the dose of nintedanib (predose) and 2 h after drug administration on Day 1; Cycle 2, Day 15: Immediately prior to swallowing the dose of nintedanib (predose) and 2 h after drug administration on Day 15.	Day1, Day15 and Day 16	No
Secondary	AUC0-12,ss,Norm (Area Under the Plasma Concentration-time Curve Between 0 and 12 Hours at Steady State, Normalised Values) of BIBF 1202 (Metabolite of Nintedanib)	AUC0-12,ss,norm (area under the plasma concentration-time curve between 0 and 12 hours at steady state, normalised values) of BIBF 1202 (metabolite of Nintedanib).; Detailed time points of sampling are: Phase I and selected phase II patients in the Nintedanib arm: Cycle 1, Day 15 to 16: Immediately prior to swallowing the dose of nintedanib (predose) and 1 hour (h), 2 h, 3 h, 4 h, 5 h, 7 h, 10 h, 12 h and 24 h after drug administration on Day 15; Cycle 2, Day 1: Immediately prior to swallowing the dose of nintedanib (predose) and 2 h after drug administration on Day 1; Cycle 2, Day 15: Immediately prior to swallowing the dose of nintedanib (predose) and 2 h after drug administration on Day 15.	Day1, Day15 and Day 16	No
Secondary	AUC0-12,ss,Norm (Area Under the Plasma Concentration-time Curve Between 0 and 12 Hours at Steady State, Normalised Values) of BIBF 1202 Glucuronide (Metabolite of Nintedanib)	AUC0-12,ss,norm of BIBF 1202 glucuronide (Metabolite of Nintedanib): Detailed time points of sampling are: Phase I and selected phase II patients in the Nintedanib arm: Cycle 1, Day 15 to 16: Immediately prior to swallowing the dose of nintedanib (predose) and 1 hour (h), 2 h, 3 h, 4 h, 5 h, 7 h, 10 h, 12 h and 24 h after drug administration on Day 15; Cycle 2, Day 1: Immediately prior to swallowing the dose of nintedanib (predose) and 2 h after drug administration on Day 1; Cycle 2, Day 15: Immediately prior to swallowing the dose of nintedanib (predose) and 2 h after drug administration on Day 15.	Day1, Day15 and Day 16	No
Secondary	Cmax,ss,Norm (Maximum Concentration of the Nintedanib in Plasma at Steady State, Normalised Values)	Cmax,ss,norm (maximum concentration of the Nintedanib in plasma at steady state, normalised values).; Detailed time points of sampling are: Phase I and selected phase II patients in the Nintedanib arm: Cycle 1, Day 15 to 16: Immediately prior to swallowing the dose of nintedanib (predose) and 1 hour (h), 2 h, 3 h, 4 h, 5 h, 7 h, 10 h, 12 h and 24 h after drug administration on Day 15; Cycle 2, Day 1: Immediately prior to swallowing the dose of nintedanib (predose) and 2 h after drug administration on Day 1; Cycle 2, Day 15: Immediately prior to swallowing the dose of nintedanib (predose) and 2 h after drug administration on Day 15.	Day1, Day15 and Day 16	No
Secondary	Cmax,ss,Norm (Maximum Concentration of the BIBF 1202 in Plasma at Steady State, Normalised Values)	Cmax,ss,norm (maximum concentration of the BIBF 1202 in plasma at steady state, normalised values).; Detailed time points of sampling are: Phase I and selected phase II patients in the Nintedanib arm: Cycle 1, Day 15 to 16: Immediately prior to swallowing the dose of nintedanib (predose) and 1 hour (h), 2 h, 3 h, 4 h, 5 h, 7 h, 10 h, 12 h and 24 h after drug administration on Day 15; Cycle 2, Day 1: Immediately prior to swallowing the dose of nintedanib (predose) and 2 h after drug administration on Day 1; Cycle 2, Day 15: Immediately prior to swallowing the dose of nintedanib (predose) and 2 h after drug administration on Day 15.	Day1, Day15 and Day 16	No
Secondary	Cmax,ss,Norm (Maximum Concentration of the BIBF 1202 Glucuronide in Plasma at Steady State, Normalised Values)	Cmax,ss,norm (maximum concentration of the BIBF 1202 glucuronide in plasma at steady state, normalised values).; Detailed time points of sampling are: Phase I and selected phase II patients in the Nintedanib arm: Cycle 1, Day 15 to 16: Immediately prior to swallowing the dose of nintedanib (predose) and 1 hour (h), 2 h, 3 h, 4 h, 5 h, 7 h, 10 h, 12 h and 24 h after drug administration on Day 15; Cycle 2, Day 1: Immediately prior to swallowing the dose of nintedanib (predose) and 2 h after drug administration on Day 1; Cycle 2, Day 15: Immediately prior to swallowing the dose of nintedanib (predose) and 2 h after drug administration on Day 15.	Day1, Day15 and Day 16	No
Secondary	fe0-12,ss (Fraction Excreted in Urine Between 0 and 12 Hours at Steady State) for Nintedanib	fe0-12,ss (fraction excreted in urine between 0 and 12 hours at steady state) for Nintedanib.; The reported value corresponds to the percentage of administered dose.	0 to 4 hours (h), 4 to 12 h, and 12 to 24 h after nintedanib	No